Vitamin D Treatment Attenuates Heart Apoptosis After Coronary Artery Bypass Surgery; A Double-Blind Randomized Placebo-Controlled Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Interleukin--10 (IL-10) Serum Level
研究概览
简要总结
Background and study aim:
Heart diseases are among the most common causes of death worldwide. A large proportion of deaths are caused by heart attacks (myocardial infarction), where blood flow to the heart is reduced resulting in damage to the heart muscle. If the arteries supplying blood to the heart start to become blocked, Coronary Artery Bypass Grafting (CABG) surgery is a treatment to replace the blocked sections of artery can reduce angina (chest pain). However, CABG surgery has complications, including an increased risk of heart attack. Vitamin D deficiency is thought to be linked to poorer recovery from heart attack and CABG surgery. This study aims to investigate if vitamin D supplementation can reduce injury to the heart following CABG surgery.
Who can participate? Adults with vitamin D deficiency undergoing CABG
What does the study involve? Participants are randomly allocated to one of two groups. Those in the first group receive vitamin D at 3 doses per day for 3 days before surgery. The second group will receive a dummy pill (placebo). Both groups will have standard CABG surgery.
What are the possible benefits and risks of participating? Those in the vitamin D group might benefit from its effects. Vitamin D has few side effects, especially when taken for only a few days.
Where is the study run from? Shahid Modarres Hospital (Iran)
When is the study starting and how long is it expected to run for? September 2017 to January 2019
Who is funding the study? Deputy of Research of Shahid Beheshti School of Medicine
Who is the main contact? Dr Erfan Tasdighi erfan.tasdighi@gmail.com
详细描述
Enrollment started in June 2018 and was completed in December 2018. The inclusion criteria were as following: the patients referred for elective and isolated Coronary Artery Bypass Graft (CABG) using Cardiopulmonary Bypass (CPB) with vitamin D deficiency (defined as 25-hydroxyvitamin D [25(OH) D] < 20 ng/mL) and normal kidney function (creatinine <1.5mg/dL). The exclusion criteria were: recent myocardial infarction, urgent CABG, non-isolated coronary surgery, redo surgery, malignant disease, presence of acute or chronic inflammatory diseases, history of vitamin D treatment within previous 6 months, or unwillingness to participate.
Intervention Following informed consent, eligible study participants were randomly assigned (by using a computer- generated random code) in a 1:1 ratio to receive either placebo or a total of 450,000 international units (IU) vitamin D3 (three 50,000 IU of vitamin D3 tablet daily for 3 days) before operation. The placebo group received three inactive medication tablets daily at the same time point. With the exception of the pharmacists, all the investigators, patients and the medical team were blinded to the group allocation.
Coronary artery bypass was done in the culprit lesions for both groups by one surgical team. The standard protocol for general anesthesia, surgical and CPB management were performed for all patients and have already been described in detail [16].
Outcome measures The primary outcome was the degree of heart apoptosis by measurement of caspase 2, 3 and 7 activity from right atrial specimen with immunohistochemistry staining, and the serum level of anti-inflammatory interleukin-10 (IL-10) and insulin- like growth factor (IGF-1), and N-terminal pro v-type Brain Natriuretic Peptide (nt-pro BNP). The biopsy from right atrial appendage was taken at the end of surgery after venous cannula removal in a nontraumatic fashion, kept into formalin and in less than 24h parafinized. Blood samples were collected at the baseline (T1), before anesthesia induction (T2), at the end of surgery after protamine reversal (T3) and the first postoperative day (T4) to measure the serum level of IGF-1, IL-10 and pro BNP. The blood samples were centrifuged at 2500 rpm for 15 min within one hour after blood sampling, and the serum was stored at -20°C until assayed.
Enzyme-linked immunosorbent assay The concentration of IL-10 was measured by a quantitative ELISA kit . The concentration of the IGF- 1 was measured by a quantitative ELISA kit .
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
With the exception of the pharmacists, all the investigators, patients and the medical team were blinded to the group allocation.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Candidate for first-time elective CABG surgery for coronary artery disease (CAD)
- •Coronary artery surgery only (i.e. no valvular surgery)
- •Cardiopulmonary pump used during surgery
- •Vitamin D level below 30 ng/ml
排除标准
- •Renal failure or creatinine level >1.5 mg/dl
- •Previous use of vitamin D supplement
研究组 & 干预措施
vitamin D
35 patients that pass the inclusion criteria and do not have exclusion criteria that will receive Vitamin D for 3 days and each time 3 doses of 50000 units
干预措施: Vitamin D (Drug)
control group
35 patients that will receive placebo for 3 days and each day for 3 doses
干预措施: Placebo (Drug)
结局指标
主要结局
Interleukin--10 (IL-10) Serum Level
时间窗: at the end of surgery after protamine reversal
The concentration of IL-10 in the serum of patients was measured using a quantitative enzyme-linked immunosorbent assay (ELISA) kit .
Caspase 2 Enzyme Level
时间窗: during the surgery, an average of 3 hours
Caspase 2 enzyme activity in right atrial specimen measured by with immunohistochemistry staining The positive control and negative control were taken from human lymph node tissue. as for the control tissue a humane lymph node was used. Positivity for active caspase is shown using cytoplasmic staining . the number of apoptotic cells was measure per each high power filed (HPF) under light microscopy.
Caspase 3 Enzyme Level, an Average of 3 Hours
时间窗: during the surgery, an average of 3 hours
Caspase 3 enzyme activity in right atrial specimen measured by with immunohistochemistry staining The positive control and negative control were taken from human lymph node tissue. as for the control tissue a humane lymph node was used. Positivity for active caspase is shown using cytoplasmic staining . the number of apoptotic cells was measure per each high power filed (HPF) under light microscopy.
Caspase 7 Enzyme Level
时间窗: during the surgery, an average of 3 hours
Caspase 7 enzyme activity in right atrial specimen measured by with immunohistochemistry staining The positive control and negative control were taken from human lymph node tissue. as for the control tissue a humane lymph node was used. Positivity for active caspase is shown using cytoplasmic staining . the number of apoptotic cells was measure per each high power filed (HPF) under light microscopy.
Interlukin-10 (IL-10) Serum Level
时间窗: Right before the intervention(3 days before surgery)
The concentration of IL-10 in the serum of patients was measured using a quantitative enzyme-linked immunosorbent assay (ELISA) kit .
Interleukin (IL-10) Serum Level
时间窗: the first postoperative day
The concentration of IL-10 in the serum of patients was measured using a quantitative enzyme-linked immunosorbent assay (ELISA) kit .
Insulin Growth Factor
时间窗: the first postoperative day
The concentration of the IGF-1 was also measured by a quantitative ELISA kit
Interleukin-10 (IL-10) Serum Level
时间窗: procedure (before anesthesia induction)
The concentration of IL-10 in the serum of patients was measured using a quantitative enzyme-linked immunosorbent assay (ELISA) kit .
次要结局
- Blood Units Usage(discharge 1 day)
- Ventilator Application(discharge 1 day)
- Hemorrhage After Surgery(immediately after surgery)
- Creatinine Level(immediately after surgery)
研究者
Erfan Tasdighi
Principle investigator
Shahid Beheshti University of Medical Sciences